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The Uptake, Distribution, and Antitumor Activity of 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea in the Murine Glioma

Laboratory of Chemical Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20014

The antitumor activity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) against the murine ependymoblastoma, glioma 26, and glioma 261 was compared with the uptake and distribution of the ¹⁴C-labeled drug in the murine ependymoblastoma. With a modified Wilcoxon rank-sum test, it was found that CCNU increased life-span in tumor animals from 2- to 4-fold, depending on the dose used and the particular tumor type studied. Uptake and distribution studies of CCNU-¹⁴C in intracerebral and subcutaneous tumors, brain adjacent to tumor, and distant (normal) brain indicated that the parent drug had relatively constant tissue/plasma ratio levels. Of the ether-soluble fractions, CCNU had a tissue/plasma ratio of greater than 4 and accounted for 15% of the ether-soluble radioactivity. From the data, it was concluded that the antitumor activity of CCNU is probably independent of preferential uptake of distribution between normal and tumor tissue. Although few conclusions concerning the mode of action of CCNU on gliomatous tumors can be made, nevertheless further consideration of its use in the treatment of human gliomas seems warranted.

Received 9/29/69. Accepted 6/ 3/70.

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